This application seeks support for an interdisciplinary postdoctoral research training program which is designed to prepare clinicians for a full-time career in cancer research and education. Support for eight postdoctoral research fellows is requested. This training grant which, in the past 21 years, provided a broad training in cancer biology and therapy, is now focused on the studies of genetic and epigenetic alterations in cancer with the ultimate goal to use these molecular changes, which are unique to cancer cells as new indicators for detection of cancer cells and specific targets for therapy. The primary purpose of this training grant is to train the physician-scientist in basic and translational cancer research. This training grant is offered as a two-year or more training program and has been a major support vehicle to provide an intensive research experience for physician trainees. The majority o f the trainees enter this program via the Cancer Center Clinical Investigations Training Program but spend all but the first clinical year (which is funded from other resources) in full-time laboratory research. The program also supports a few selected applicants who apply to this training program (physicians and Ph.D.s) because they are interested in molecular changes and targets in specific fields of cancer research. Only the most qualified and outstanding applicants are selected for these few positions. The training faculty who serve as mentors for individual trainees in this program are acknowledged leaders in their field. Examples include, but are not limited to, Drs. Vogelstein and Kinzler (genetic changes in progression of cancer), Baylin and Herman (role of methylation in progression of cancer), Isaacs and Davidson (molecular biology of prostate and breast cancer) and Pardoll and Jaffee (novel approaches to cancer vaccines). In addition a close interaction between the faculty of this training program with other graduate and postgraduate training programs in basic science in the School of Medicine provides comprehensive exposure to basic aspects of cancer biology. As part of their training curriculum, trainees are required to complete two courses in the basic aspects of cancer biology and therapy, and actively participate in ongoing seminars, including a presentation of their research at Fellows Research Day. Mentors monitor the trainee's research progress while continuously emphasizing ethical and responsible conduct of research.